Article on Metastasis

[Laurettas]

Want to understand why cancer cells metastasize? Think of Sparta. Ancient Greek warriors were fed a special diet that better prepared them for the demands of battle on distant fields. Cancer cells that metastasize may do the same thing according to a new study revealing previously unknown differences between cancer cells that continue to grow at the original tumor site, and those that travel to other organs.

Given that a cancer cell's unyielding ability to metastasize is the primary cause of cancer-related death, understanding how they successfully migrate can be lifesaving.

Scientists at The University of Texas MD Anderson Cancer Center have found that cancer cells traveling to other sites have different energy needs from their "stay-at-home" siblings which continue to proliferate at the original tumor site. The study results are in the Sept. 21 online edition of Nature Cell Biology.

The reason may lie with the protein, PGC-1α, a type of transcription co-activator crucial to regulation of cellular metabolism. PGC-1α appears to play a role in how cancer cells are able to acquire unique energy sources that allow them to travel and spread cancer in the body.

"New therapy strategies are beginning to focus on the unique vulnerabilities of cancer cell metabolism. Determining the metabolic requirements of invasive cancer cells could be of therapeutic value," said Valerie LeBleu, Ph.D., assistant professor of cancer biology at MD Anderson and lead author of the Nature Cell Biology paper. "We found that invading cancer cells rely on mitochondria during their transition to other cancer sites."

Cancer cells use PGC-1α to stimulate the growth of new mitochondria, the cell's "power plants" that generate ATP, an energy "currency" used by cells to grow. Metastasizing cells also rely on PGC-1α for a process known as oxidative phosphorylation that boosts ATP during the cell's journey to other sites. If mitochondria is the kitchen, then PGC-1α is the chef, ATP the entreé and oxidative phosphorylation a key ingredient. This overall process, mitochondria respiration, allows some cancer cells to harness the required energy to survive the hostile journey through tumor and normal issue, blood vessels, and entry into new organs.

In other words, some cancer cells are programmed to eat at home, while others have a special diet that allows them to travel to other sites. If there was a therapeutic way to stop the migrating cells from packing a lunch ahead of time, it could potentially halt their journey. Suppressing PGC-1α appears to accomplish this.

"The most dangerous cancer cells are the ones that can efficiently move and find a new home," said Raghu Kalluri, M.D., Ph.D., chair of cancer biology and an investigator on the study. "The study revealed a strong correlation between PGC-1α expression in invasive cancer cells and the formation of distant metastases in breast cancer patients."

More information: αPGC-1 mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis, Nature Cell Biology, DOI: 10.1038/ncb3039


Provided by University of Texas M. D. Anderson Cancer Center



"Cancer cells adapt energy needs to spread illness to other organs." September 21st, 2014. http://medicalxpress.com/news/2014-09-c ... lness.html

[peanut_8]

Very interesting.

[KWT]

Cool, more shit we can't understand.

[Kiwi Debz]

Ha ha Kenny .... You are so right .... There is so much stuff that I am having a head spin .... How the hell are we meant to know all this stuff ?....

Deb

[Laurettas]

The thing I found interesting was their finding that mitochondria are the parts of a cell that cause it to move--metastasize. There have been those who have been using drugs to focus on the mitochondria--the one in Alberta, three initials, can't remember the name of the drug, darn it! Anyhow, maybe they are on the right track and we need to be looking at drugs that affect the mitochondria of cells.

[CRguy]

There have been those who have been using drugs to focus on the mitochondria--the one in Alberta, three initials, can't remember the name of the drug, darn it!

DCA ?

A phase I study published in January 2007 by researchers at the University of Alberta, who had tested DCA on human cancer cells grown in mice,[15] found that DCA restored mitochondrial function, thus restoring apoptosis, allowing cancer cells to self-destruct and shrink the tumor.[16]

from the Wiki article http://en.wikipedia.org/wiki/Dichloroacetic_acid

[wandalein]

DCA? Dichloro Acetic Acid (DCA). It is approved by Health Canada and was discovered at the University of Alberta.

[GrouseMan]

DCA was first described in Ann 173 p288 in 1874. Its been around for a very long time. Mostly as an topical astringent. Its a pretty strong organic carboxylic acid and I wouldn't want to take it unless it was well buffered, such as the sodium salt or some such. It would likely get metabolized pretty quickly in vitro. I read some of the papers some time ago about using this in cancer treatment and I don't think it has much of an effect really. I don't think the lab small animal results translated well to people. It would not only effect tumor mitochondria but also normal cells as well. It's reported LD 50 in Rats is 2.82 g/kg body weight. So its not exactly benign.

See the Merck Index 9th edition entry 3021.

You can buy a Kg of the stuff from Aldrich Chemical Company for $52.40 (My Latest Catalog is from 2010). So its cheap as dirt really. Its a liquid as the free acid at room temp, but like I said I wouldn't use it as such.

From the Wiki Article - This is what really turned me off to it:

"In 2010, it was found that for human colorectal tumours grown in mice, under hypoxic conditions, DCA decreased rather than increased apoptosis, resulting in enhanced growth of the tumours.[22] These findings suggest that at least in some cancer types DCA treatment could be detrimental to patient health, highlighting the need for further testing before it can be considered a safe and effective cancer treatment"

GrouseMan

[Laurettas]

That was it, CRGuy--DCA. And, Grouseman, I had forgotten about that fact concerning colon cancer. Sigh, too bad. Do you know any more about mitochondria being responsible for metastasis? Would love to hear your thoughts.

[GrouseMan]

No, I don't think it has anything to do directly with metastases. Every cell has a Mitochondrion if not multiple ones. They are the principle energy producer for for cells. It is just that in tumors, they may have defective ones or since they proliferate and turn over so much faster than normal cells interfering with them may but not always many result in the cancerous cells being pushed into apoptosis, when in general they seem to avoid it. This is just another potential area of research right now to see if mucking up the works of the mitochondria, might kill cancer cells more selectively than normal tissue cells.

See:.

http://en.wikipedia.org/wiki/Mitochondrion

I personally subscribe to the idea that mets result primarily from migration and infiltration into tissues by cancer stem cells when they find environments that are suitable for them to move out of a sort of stasis state into an active state. These stem cells are basically inert to chemo therapy, and the immune system because they are not using energy, are not producing signaling proteins. The primary and other mets will produce many of these CSC's that circulate until they find the suitable environment to start proliferating(multiplying).

Much more research needs to be done concerning the ability to kill these CSC's in my opinion.

GrouseMan

[wandalein]

My husband who was thankfully NED at this 3 month followup from liver resection was considering DCA. I have read a lot about it. It may not be the magic bullet. It seems that cancer is a tricky thing. The DCA has shown success in a lot of cases and those are thought to be the glucose uploading cells feeding off sugar, the ones that are seen on a PET scan. However there is a theory and some evidence to suggest, and one I would not want to check out, that it misses or causes the morphis of the oxygen uploading cancer cells. These are the ones that will migrate and thrieve in the brain. My husband is taking Oncolyn and that is less expensive and seems to show promise as well.

[Cb75]

DCA can work. My ND has a stage IV melanoma patient in remission using it. The biggest issue is permanent neuropathy.....many of us are familiar with that.

cb